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First truly artificial organism engineered

The world’s first truly artificial organism has been engineered by researchers in California. The bacterium makes an amino acid that no other organism uses to build proteins.

The work is being hailed as “a very great accomplishment” and the technique promises to open unique avenues for manufacturing drugs.

Amino acids are the fundamental building blocks of life, making up the proteins which constitute all living cells. The DNA of every organism on Earth contains three-letter codes, known as codons, for 20 such amino acids.

Now, a team led by Peter Schultz of the Scripps Research Institute in La Jolla has managed to coax E. coli bacteria to produce a 21st amino acid and use it to make a protein, using only natural food sources such as sugar and water.

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Stolen genes

Schultz’s team combined many different techniques to achieve their goal. First, the researchers made the bacteria produce the new amino acid, p-aminophenylalanine (pAF). For this they stole genes from other bacteria that make pAF as a secondary metabolite and added them to the E. coli bacteria.

Next, the team had to make the bacteria’s protein-making machinery recognise pAF. They evolved a mutant E. coli strain that had a specific combination of transfer RNA and the enzyme synthetase, which could grab pAF for the protein factory whenever it encountered a particular termination codon. This amber codon normally signals the end of a gene, and therefore protein synthesis, but is rarely used by the bacteria.

Finally, they inserted into the bacteria a sperm whale gene that codes for the protein myoglobin. The gene was first modified by adding the amber codon in places known not to affect the protein. With all these changes in place, the bacteria started producing myoglobin with pAF incorporated exactly where intended.

“We had to make it work just like all the other 20 amino acids,” says team member Ryan Mehl, formerly at Scripps and now at the Franklin and Marshall College in Lancaster, Pennsylvania. “This is the first time anyone has ever combined all these and had a healthy, reproducing organism indistinguishable from a natural organism.”

Unnatural selection

Hiroaki Suga, of the University of Buffalo in New York, agrees. Suga, an expert on techniques of evolving catalytic RNA to produce non-natural amino acids in the lab, told New Scientist&colon; “The result is amazing. It’s a very great accomplishment.”

It is not yet clear what advantage, if any, the 21st amino acid confers on the bacteria. Schultz’s team is putting the modified bacteria through its paces to see if they can out-compete natural ones, at least in the lab.

But even if they do, there is no fear of these bacteria running amok in the wild, says Mehl. They are special research strains that cannot live without the nutrients supplied in the lab.

Cheaper and more efficient

The technique should help engineer proteins to make better drugs. Normally, pharmaceutical companies have to modify natural enzymes to stabilise them for use as drugs.

But if bacteria, or even higher organisms, can be genetically engineered to produce new amino acids that make longer-lasting and more effective enzymes, drug production could become more efficient and cheaper, says Mehl.

And there is no reason to stop at 21 amino acids. “In theory, the sky is the limit,” he says.

Journal reference&colon; Journal of the American Chemical Society (DOI&colon; 10.1021/ja0284153)